Project Summary: This is an application for a K23 award for Dr. Carmen A. Peralta, who proposes a novel, multi-disciplinary approach to understanding racial/ethcnic disparities in kidney function decline. This award will allow Dr. Peralta the resources and protected time to achieve the following career development goals: (1) to become an independent, translational clinical researcher in the field of racial/ethnic disparities in kidney disease; (2) to become an expert in the application of genetic epidemiology methods to study these differences; and (3) to utilize sociodemographic measurements to improve understanding of the complex mechanisms involved in these disparities. To achieve these goals, Dr. Peralta has assembled a mentoring team comprised of her sponsor and primary mentor, Dr. Michael Shlipak (an expert in the field of cardiovascular complications of early kidney dysfunction), and two co-mentors: Dr. Neil Risch (a genetic epidemiologist) and Dr. Paula Braveman (an expert in social determinants of health). The epidemic of kidney disease currently affects 13% of U.S. adults, and the progression to end stage renal disease (ESRD) affects minorities disparately. African-Americans and Hispanics are the fastest grow- ing groups in the ESRD population. Despite well-documented disparities in progression of advanced kidney disease to ESRD, no studies have evaluated the incidence of chronic kidney disease (CKD) or early kidney function decline in the US across racial/ethnic groups. It is unknown whether certain racial/ethnic groups have an increased genetic predisposition due to a common genetic ancestry or whether social or environ- mental factors explain observed differences. Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), Dr. Peralta will compare rates of kidney function decline and incident CKD across four major racial groups and test possible genetic and sociodemographic mechanisms to explain these differences. Three specific aims are proposed: Aim 1: To compare rates of kidney function decline and incident chronic kidney disease across four major racial/ethnic groups (Caucasians, African-Americans, Hispanics, and Chinese- Americans) using creatinine and cystatin C based measures; Aim 2: To evaluate whether genetic ancestry is an independent predictor of kidney function decline and incident chronic kidney disease within racial groups and to explore gene-environment interactions in kidney function decline and incident kidney; and Aim 3: To evaluate the association of individual and neighborhood-level socioeconomic characteristics with kidney function decline and incident kidney disease across racial groups. Relevance: A better understanding of the mechanisms involved in racial/ethnic disparities in kidney function decline at earlier stages of kidney dysfunction could lead to important interventions and prevention strategies in halting this costly epidemic. .